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Research in Biomedical Optics

Highlights: OPPORTUNITY for Independent diagnostic spectroscopy projects

Research in Biomedical Optics and Spectroscopy

Biomedical applications of lasers and laser spectroscopy are changing the face of medicine as it is currently practiced. The mission of the Laser Biomedical Research Center (LBRC), an NIH-sponsored research resource center, is to develop the scientific understanding required for advancing the applications of lasers in medicine and biology. Research projects are developed from the ground up: fundamental studies involving biochemicals, cells, ex vivo tissue are undertaken to advance understanding, spectral models are developed and instrumentation refined, before these methods are tested in clinical trials at medical centers and hospitals.

Biomedical initiatives within the LBRC have resulted in the development of new spectroscopic methods to diagnose disease through minimally invasive procedures using absorption, fluorescence, Raman and intensity-based light scattering techniques; novel technologies for spectroscopic imaging of disease, in particular field-based light scattering techniques such as low-coherence interferometry; and improved understanding and modeling of light transport in tissue. Basic studies in biophysics and biochemistry are also pursued to support the development of novel spectroscopic methods of disease diagnosis.

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Highlights:

The MIT Laser Biomedical Research Center (LBRC) announces the availability of spectroscopic instruments for projects of outside investigators aimed at developing novel diagnostic applications and demonstrating their feasibility in clinical translational studies. Two instruments will be made available for this purpose: (1) a “mini-FastEEM”, capable of collecting diffuse white light spectral reflectance and 340 nm-excited fluorescence; and (2) a Raman spectroscopy instrument capable of collecting Raman spectra from biological tissues over the fingerprint range (400-1960 cm-1). Both instruments collect spectra in ~1 s by means of specially designed optical fiber probes that sample 1 mm2 regions of tissue. Specially designed display and spectral analysis software are built in.

Purpose and Scope of the Program: The purposes of the LBRC outside user diagnostic instrumentation program are: (1) to foster clinical translational research in optical spectroscopy; and (2) to familiarize young/new investigators with the methods of diagnostic spectroscopy. The program particularly favors focused clinical projects with well-defined endpoints. Potential investigators with medical credentials are specially encouraged to participate. The LBRC will provide instruments, optical fiber probes, training, instrumentation support and troubleshooting, and support for data analysis as necessary. The research may be performed at the applicant’s institution, at MIT, or a combination of the two.

Eligibility: Both new and established investigators may apply. New investigators are specially encouraged to use this opportunity to collect preliminary data for subsequent independent funding. Funded investigators must demonstrate how the use of these instruments will represent a departure from their ongoing work.

Application Guidelines: Applications will be accepted on a rolling basis using guidelines detailed for the LBRC outside projects. Please see http://web.mit.edu/spectroscopy/facilities/guideline.html for detailed information and an application form.

Responsibility of the Awardees: Awardees must submit a written progress report (2 page NIH format) within three months of the completion of their project. In addition, awardees may be invited to present their work at an LBRC Advisory Committee meeting or an NIH site visit. The LBRC must be acknowledged on all publications and presentations of the research in the form of “Supported in part by the MIT Laser Biomedical Research Center, NIH Grant P41-RR02594.”

(1) mini FastEEM: Clinical instrumentation

“mini-FastEEM”, capable of collect¬ing diffuse white light spectral reflectance and 340 nm-excited fluorescence.

schematic
Figure 1. Schematic of clinical FastEEM instrument.

The DRS/IFS instrument uses two different light sources including a 337 nm N2 laser (NL100, Stanford Research Systems, Sunnyvale, CA) for fluorescence spectroscopy and a Xe lamp (L7684, Hamamatsu Corp., Bridgewater, NJ) for reflectance spectroscopy. The Xe lamp provides a 2.9 µs FWHM pulse of white light, 1 J/pulse max, given an external trigger supplied by the software. The N2 laser provides a 3.5 ns FWHM pulse of 337 nm light, 170 µJ per pulse. Light is delivered and collected from tissue via FastEEM probe and is brought to the entrance slit of the diffraction grating spectrometer (Spectra Pro 150, Acton Research, Acton, MA). The collected light is dispersed onto an intensified CCD detector (PIMAX, Roper Scientific, Princeton, NJ). To insure easy reproducibility, the collection fibers have individual SMA adapters that connect to the spectrograph. The CCD is operated in a gated mode and is thermoelectrically cooled to -20C. The total collection time for fluorescence and reflectance spectra is approximately 0.3 s. Several of these acquisitions can be averaged together to increase the SNR, making a typical acquisition time on the order of 1.5 s. Integrated software (LabVIEW and Matlab) in the system enables rapid collection of DRS and IFS spectra.

schematic
Figure 2. Example of DRS and IFS spectra acquired in 1.5s from breast tissue.

Recent Publications

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari and M. S. Feld, "Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy," J Biomed Opt 13 (2), 024012 (2008)

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari and M. S. Feld, "Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy," J Biomed Opt 11 (2), 021007 (2006)

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam and M. S. Feld, "NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes," Cancer Res 62 (3), 682-687 (2002)



(2) Raman spectroscopy instrument

Raman spectroscopy instrument capable of collecting Raman spectra from biologi­cal tissues over the fingerprint range (400-1960 cm-1).

schematic
Figure 1.Schematic of clinical Raman instrument.

The new system will measure approximately 32” x 17” x 10” and sit on a low wheeled platform. The instrument uses an 830 nm diode laser, delivered through the probe, to excite Raman scattering. The probe delivers to and collects light with the probe tip in contact with tissue. Light from an 830 nm InGaAs diode laser (Process Instruments, Salt Lake City, UT) is passed through a holographic bandpass filter centered at 830 nm (Kaiser Optical Systems Incorporated, Ann Arbor, MI). The light is then collimated and coupled into the 200 μm core diameter excitation fiber of the Raman probe. Illumination of the sample is gated by a high-speed, 6 mm aperture, computer-controlled shutter (LS6ZM2, Vincent Associates, Rochester, NY). The excitation fiber is terminated with an FC connector to provide day-to-day reproducibility of alignment. For 100 mW of excitation power, the resultant irradiance is 318 W/cm2 which has been clearly shown to not cause any tissue damage. The proximal end of the probe contains the collection fibers that are arranged in a vertical array and serve as the entrance slit to the spectrograph (Holospec f/1.8i, Kaiser Optical Systems), attached by means of a modified BNC connector. The collected Raman light is dispersed onto a back-illuminated, deep-depletion CCD detector with a 1024×256 array of pixels. The CCD detector is thermoelectrically cooled to -70C. The probe is 4 m long and is 2 mm in overall diameter. Integrated software (LabVIEW and Matlab) in the system enables rapid collection of Raman spectra (1s) and real-time analysis of the spectral parameters.

data
Figure 2.Typical Raman spectrum acquired in 0.5s from breast tissue.

Recent Publications

S. Haka, Z. Volynskaya, J. A. Gardecki, J. Nazemi, J. Lyons, D. Hicks, M. Fitzmaurice, R. R. Dasari, J. P. Crowe and M. S. Feld, "In vivo margin assessment during partial mastectomy breast surgery using raman spectroscopy," Cancer Res 66 (6), 3317-3322 (2006) URL: http://cancerres.aacrjournals.org/cgi/reprint/66/6/3317.pdf.

S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari and M. S. Feld, "Diagnosing breast cancer by using Raman spectroscopy," Proc Natl Acad Sci U S A 102 (35), 12371-12376 (2005) PMCID: PMC1194905.

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari and M. S. Feld, "Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy," J Biomed Opt 11 (2), 021007 (2006)

J. T. Motz, M. Fitzmaurice, A. Miller, S. J. Gandhi, A. S. Haka, L. H. Galindo, R. R. Dasari, J. R. Kramer and M. S. Feld, "In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque," J Biomed Opt 11 (2), 021003 (2006)

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Currently, the LBRC has core and collaborative projects in the following areas.

Core Projects:

Collaborative Projects:
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